Retractable brush for use with endoscope for brush biopsy

ABSTRACT

A retractable brush structure is attached to a cylindrical rigid rod which in the closed position passes through a channel in an endoscope. After the closed brush passes through the endoscope, the brush is opened and moves transversely to the tissue in order to remove cells from an area under examination. The brush is closed and withdrawn from the endoscope and sample tissue is removed from said brush for examination after it is withdrawn from the endoscope.

FIELD OF THE INVENTION

The present invention is directed to a method and apparatus forobtaining transepithelial specimens of body surfaces using anon-lacerating technique. Specifically, the invention is directed toretractable tools such as a brush, used with endoscopes, for samplingsquamous epithelium from lesions found from the nose to the throat andin similar body tissues. The invention is also directed to an improvedapparatus for non-lacerational testing of lesions that involve theepithelium of the nasopharynx, hypopharynx, pharynx, trachea, larynx,and the upper esophagus.

BACKGROUND OF THE INVENTION

Cancers of the oral cavity and pharynx are a major cause of death fromcancer in the U.S., exceeding the U.S. death rates for cervical cancer,malignant melanoma and Hodgkin's disease. According to the AmericanCancer Society's Department of Epidemiology and Surveillance, anestimated 30,750 new cases of oral cancer were diagnosed in the U.S.during 1997, a figure which accounts for 2% to 4% of all cancersdiagnosed annually.

Despite advances in surgery, radiation, and chemotherapy, the mortalityrate of oral cancer has not improved in the last 20 years. Ultimately,50% of patients die from their malignancy, and 8,440 U.S. deaths werepredicted for 1997. There are several reasons for the high mortalityrate from oral cancer, but undoubtedly, the most significant factor isdelayed diagnosis. Studies have demonstrated that the survival and curerate increase dramatically when oral cancer is detected at an earlystage. For example, the 5-year survival rate for patients with localizeddisease approximates 79% compared to 19% for those with distantmetastases. Unfortunately, approximately two thirds of patients at timeof diagnosis have advanced disease, and over 50% display evidence ofspread to regional lymph nodes and distant metastases.

Delay in the diagnosis of oral and pharynx cancer is often the result ofthe limited diagnostic tools available in the prior art. The dentist orphysician who detects such a lesion which is not clearly suggestive of aprecancer or cancer clinically, and who is limited to the prior arttools and methods, is faced with a quandary. Approximately 5-10% ofadult patients seen in a typical dental practice exhibit some type oforal lesion, yet only a small proportion (approximately 0.5% to 1%) areprecancerous or cancerous. These oral lesions are commonly evidenced asa white or reddish patch, ulceration, plaque or nodule in the oralcavity. The overwhelming majority of these lesions are relativelyharmless; however, the multitude of poorly defined lesions in the oralcavity can be confounding to the clinician. A diverse group of orallesions may be easily confused with malignancy, and conversely,malignancy may be mistaken for a benign lesion. Benign tumors, reactiveprocesses, traumatic lesions, oral manifestations or systemic diseases,inflammatory oral disorders, and bacterial, viral and fungal infectionsall display similar oral features thereby impeding establishment of anaccurate clinical diagnosis.

The only reliable means currently available in the prior art todetermine if a suspect oral lesion is pre-cancerous or cancerous, is toincise or excise (i.e. lacerate) the lesion surgically with either ascalpel or a laser so that a histological section of the removed tissuecan be prepared for microscopic evaluation. Histology can be generallydefined as the microscopic inspection or other testing of a crosssection of tissue. This prior art form of oral surgical biopsy isgenerally performed by a surgeon, and is often inconvenient, painful,and expensive.

Since the majority of oral abnormalities detected clinically provebenign when tested microscopically, and given the limitations of biopsy,including cost, inconvenience, pain and potential for complications,relatively few oral lesions are subjected to biopsy. It is primarily forthis reason that only oral lesions with clinical features stronglysuggestive of cancer or precancer are referred for biopsy as describedin the prior art. As a result, many patients with ominous, but visuallyless suggestive lesions are allowed to progress to advanced oral cancer,with their condition undiagnosed and untreated.

The oral epithelium is substantially identical to the epithelium of thenasopharynx, hypopharynx, pharynx, trachea, larynx, and the upperesophagus. As a result, otolaryngology currently suffers from theeffects of the same diagnostic dilemma which affects dentistry, i.e. theinability to clinically distinguish between common benign-appearinglesions and identically appearing pre-cancerous and early cancerouslesions. Thus, the only two cancers in the U.S. which have not improvedin mortality in the last thirty years are oral cancer and laryngealcancer.

In many environments including those identified above, endoscopes areused to examine interior parts of the body which are inaccessible toordinary visual observation. Observation of these inner parts with anendoscope is for purposes of locating pathological areas, trying toidentify them using the endoscopic visual instrument and determining howto diagnose and treat such visualized areas.

Potential abnormalities in various portions of the body may be apparentto a visual observer because of certain lesions appearing at thevisualized tissue in the organ or area being observed.

Common, benign-appearing nose and throat lesions are usually noticed bythe otolaryngologist during a routine, office examination of the throatwhich is typically conducted using a type of endoscope, known as aflexible nasopharyngoscope. This thin optical tube is easily threadedfrom the patent's nose into the throat and requires only a localanesthetic sprayed into the nose. This routine office procedure isperformed by the average otolaryngologist many times each day.

The diagnostic dilemma for the otolaryngologist that is posed by theidentical appearance of benign and pre-cancerous lesions is actuallymore acute than it is for the dentist. Although invasive and thereforeavoided, a scalpel biopsy of the oral cavity is typically performed asan office procedure. Only local anesthetic is required, and bleedingfrom a scalpel biopsy of the oral cavity does not pose any aspirationdanger. In contrast, a scalpel biopsy in many areas of the throat cannotbe performed as an office procedure. This is because a scalpel biopsy inmany areas of the throat may result in potentially dangerous aspirationof blood if the procedure is not performed under general anesthesia.

Referral of the patient for an operating room procedure requiringgeneral anesthesia is both expensive and intrusive, and may expose thepatient to other risks such as anesthesia and infection risk. Theotolaryngologist is therefore hesitant to scalpel biopsy mostbenign-appearing throat lesions although they may represent the mosttreatable stage of a pre-cancer or cancer.

In many body sites, but not the oral cavity, a technique known ascytology is commonly utilized as an alternative to performing alacerating biopsy and histological evaluation. In these body sites,pre-cancerous and cancerous cells or cell clusters tend to spontaneouslyexfoliate, or “slough off” from the surface of the epithelium. Thesecells or cell clusters are then collected and examined under themicroscope for evidence of disease.

Since prior art cytology is directed towards the microscopic examinationof spontaneously exfoliated cells, obtaining the cellular sample isgenerally a simple, non-invasive, and painless procedure. Exfoliated orshed cells can often be obtained directly from the body fluid which iscontiguous with the epithelium. Urine can thus be examined for evidenceof bladder cancer, and sputum for lung cancer. Alternatively, exfoliatedor shed cells may be obtained by gently scraping or brushing the surfaceof a mucus membrane epithelium to remove the surrounding mucus using aspatula or soft brush. This is the basis for the well known procedureknown as the Pap smear used to detect early stage cervical cancer.

Because of the ease by which a cellular sample can be obtained fromthese body sites, prior-art cytology is typically utilized to screenasymptomatic populations for the presence of early stage disease. In thecervical Pap smear, for example, the entire surface area of the cervicalregions where cancer generally occurs is gently scraped or brushed tocollect and test the mucus from those regions. Abrasion of theunderlying cervical epithelium is undesired, as it can cause bleedingand discomfort to the patient. This procedure is thus typicallyperformed when no particular part of the cervix appears diseased, andwhen no suspect lesion is visible.

The design of prior art cytology sampling instruments reflects their useto sweep up cells which were spontaneously exfoliated and present on thesuperficial epithelial surface. Since prior-art cytology brushes needonly to gently remove surface material, they are designed of varioussoft materials which can collect the cervical mucous with minimalabrasion to the underlying epithelium. These cytology samplinginstruments therefore either have soft bristles, soft flexiblefimbriated or fringed ends, or even, as in the case of the cotton swabor spatula, no bristles at all.

Examples of prior art cytological sampling tools include the wooden,metal or plastic spatula. According to the traditional method of Papsmear sampling, the spatula is placed onto the surface of the cervix andlightly depressed or scraped across the surface of the cervix to pick upexfoliated cells.

Further examples of prior art cytological sampling tools include theCytobrush®; a device which uses soft and tapered bristles to sample shedcells from the cervical canal. U.S. Pat. No. 4,759,376, which allegedlycovers this product, likewise describes a conical tapered soft bristlebrush (a mascara brush shape) which is placed into the cervical canaland rotated for endocervical sampling. U.S. Pat. No. 4,759,376 teachesthat the bristles “are to be relatively soft such as that of a softtoothbrush to more readily bend and avoid damaging the tissues.” By wayof further example, physicians have long used the common swab,commercially known as the Q-Tip®, to perform endocervical sampling.

Other prior art cytological sampling tools designed to obtain acytological sample from the cervix may combine both endocervical andexocervical sampling regions into one device. These devices swab thesurface of mucous-covered tissue by soft brushing the mucous layer ofthe endocervix and exocervix at the same time, thereby collecting thecells contained in the mucous layer tissue of those surfaces. Thesedevices include the Unimar®-Cervex Brush™, a brush that has a contouredflat comb-like head with a single layer of flexible plastic bristles(similar to a flat paint brush having only one row of bristles) in whichthe center bristles are longer than the bristles on the ends. Accordingto the method of use for the device, the center bristles are insertedinto the cervical canal until the lateral bristles bend against theexocervix. The device is then removed and the cells are swabbed across amicroscope slide similar to painting with a paintbrush.

Similarly, the Bayne Pap Brush™, which Medical Dynamics, Inc. representsis covered by U.S. Pat. No. 4,762,133, contains a center arm, made ofsoft DuPont bristles, running horizontal to the cervical canal and asecond arm of soft bristles at ninety degrees to the first arm, creatingan L-shape. The center arm is placed within the cervical canal and thenrotated. Upon rotation, the soft bristles of the second armautomatically sweep the surface of the exocervix in a circular motionthereby sampling the exocervix along with the endocervix.

Although cytology has been adopted for use in several other body sites,it has not been found useful to test questionable lesions of the oralareas. This is in large part due to the fact that the prior art devicesand methods used to obtain a cellular sample for cytology areunsatisfactory when used to sample lesions of the oral and nasal areasand areas containing similar epithelia. Unlike the uterine cervix,questionable lesions of the oral cavity and similar epithelia may betypically coated with multiple layers of keratinized cells. This“keratin layer” forms a relatively hard “skin-like” coating over thesurface of the lesion and may thus hide the abnormal cells lyingunderneath it and prevent their exfoliation from the surface.

As noted above, the design of prior art cytology sampling instrumentsreflect their use in tissues where spontaneously exfoliated abnormalcells are commonly present on the surface of an area of epithelium thatharbors disease. These cytology sampling instruments therefore eitherhave soft bristles, soft flexible fimbriated ends, or even no bristlesat all. Since prior-art cytology brushes only need to gently removesurface material, they are designed of various soft materials which cancollect the cervical mucous with minimal abrasion to the underlyingepithelium.

While abnormal cells can spontaneously exfoliate to the epithelialsurface and be gently removed by prior art instruments in the uterinecervix and other similar tissues, in many oral cavity lesions theabnormal cells never reach the surface because they are blocked by thekeratin layer. This limitation is a major cause of the high falsenegative rate of prior art cytological testing to detect lesions of theoral cavity. That is, a large proportion of oral lesions found to bepositive using lacerating biopsy and histology are found to be negativeusing cytology. In one major study, this false negative rate was foundto be as high as 30%.

It is largely due to this lack of correlation between histology andprior art oral cytology that there is currently no significant use oforal cytology in the United States or elsewhere to test questionableoral lesions. Since it is well known that dangerous, truly cancerousoral lesions may commonly be reported as “negative” using prior artcytologic sampling techniques, prior art cytologic techniques offerlittle as a reliable diagnostic alternative to the lacerating biopsy andhistology.

SUMMARY OF THE INVENTION

An object of the present invention to provide an apparatus and methodfor sampling epithelial cells from the anatomy without the pain orinjury of lacerational biopsies.

Another object of this invention is to provide a brush biopsy deviceconveniently used with endoscopes so as to effectively sample tissue ina questionable area without needing a lacerational technique.

A further object of the present invention to provide an apparatus forsampling epithelial tissue in the nasopharynx, hypopharynx, pharynx,trachea, larynx, and the upper esophagus.

Still another object of this invention includes utilizing such a brushtechnique for use with endoscopic examination in any area in whichsampling of questionable tissue through non-lacerational techniquesprovide an enhanced medical procedure as contrasted with currentlacerational techniques employed.

It is a further object of the present invention to provide anon-lacerating apparatus which may readily sample cells from all levelsof a surface epithelial lesion, including the basal, intermediate andsuperficial layers of the lesion.

Other objects and advantages and features this invention will becomemore apparent from the following description.

In accordance with the present invention, an apparatus is provided forsampling all types of epithelium, particularly squamous epithelium, fromlesions found in the nasopharynx, hypopharynx, pharynx, trachea, larynx,and the upper esophagus. Further, in accordance with the invention, animproved method is provided for testing questionable lesions found inthe epithelium of the nasopharynx, hypopharynx, pharynx, trachea,larynx, and the upper esophagus and other body tissues. The methodinvented involves exerting sufficient pressure in the lesion area with asurface or edge capable of dislodging cells in and under a keratinizedlayer.

For purposes of this patent application, the prior art scalpel procedureis defined as lacerational, whereas the novel invention herein isnon-lacerational and therefore minimally invasive. To the extent that anabrasive brush has characteristics that may cause minor discomfortand/or bleeding, there is substantial difference between the prior artscalpel trauma and the minimal trauma associated with the presentinvention.

The above and other objects are accomplished by providing a channel inthe longitude interior of an endoscope through which a retractable brushmay pass. The brush is formed so as to be closed as it passes throughthe endoscope and is opened after passing through the endoscope when inthe appropriate location. The brush is capable of being rotated andmoved against the tissue so as to remove suspect tissue, and the brushis then closed and withdrawn from the endoscope. The tissue collected bythe brush is then ultimately examined for potential cancerous orpre-cancerous conditions in accordance with well known cell examinationtechniques.

Focal sampling of questionable lesions of the nose and throat areas andof similar epithelia is provided using a stiff-bristled brush. Byrubbing harder than normal cytological sampling and using a stiff devicewhich penetrates epithelium, one can reach to the basement membranewithout lacerating. As opposed to the prior art, use of the deviceallows cell sampling which can readily and consistently produce atrans-epithelial cytologic sample. That is, by utilizing the inventiondisclosed herein, cells can readily and consistently be obtained fromall levels of the epithelium (basal, intermediate and superficial) of asuspect lesion, thus overcoming the limitation in the prior art ofabnormal epithelial cells being inaccessible to cytology for a varietyof reasons, including because they are covered by a keratin layer. Theresulting cellular sample functionally approximates the cellular sampleof a lacerating biopsy device but is obtained with the ease of a stiffbrush sweeping and without discomfort to the patient. The subjectinvention therefore makes practical the routine testing of questionablelesions of the nasopharynx, hypopharynx, pharynx, trachea, larynx, andthe upper esophagus, thus allowing early detection and treatment ofcancer and pre-cancer of those areas.

While the preferred embodiment has been described with respect to abrush, the present invention generally describes a method and apparatusfor obtaining transepithelial specimens of a body surface. The inventionrelates to a non-lacerational method and apparatus to obtain such aspecimen. The reason one seeks to obtain a transepithelial sample isbecause suspect cells appear at the superficial layer of the epitheliumoriginate at the basal layer within the tissue. With respect to thenasopharynx, hypopharynx, pharynx, trachea, larynx, and the upperesophagus, basal cells originate in the general area of the basementmembrane separating the epithelial tissue from the tissue below themembrane known as the submucosa. In determining whether or not a patienthas a precancerous or cancerous condition, it is important to reach downto the basement membrane and slightly therebelow because metastases maybe suspected depending on the cellular architecture existing at justbelow or at the basement membrane through to the superficial layer.

The structure of the brush and bristles including the stiffness thereofas well as the shape of the bristle tips contribute to the effectivenessof the brushing or scrubbing action in retrieving cells from thetransepithelial layers. The shape of the bristle tips is determined bythe bristle cutting process. The bristle tips, preferably, have scrapingedges. The tips of the brush and the brush itself may be considered asan assemblage of penetrating edges.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partial perspective and sectional view illustrating theretractable brush in an open position after passing through theendoscope.

FIG. 2 is an exploded partial perspective and sectional view showing thehandle manipulating the brush and illustrating the retractable brushfolding together as it is drawn into the endoscope.

DETAILED DESCRIPTION

The prior art has used brushes with endoscopes to sample the examinedarea by moving the bristles of the brush across the suspect tissue area.Such brushes are similar to those described above which remove cellsfrom the superficial layer, and the bristles do not penetrate below suchlayer because there is no direct force applied pushing tips of thebristles into the tissue being examined. Further, the prior art brushesmerely rub against the surface and the brush area is very limited. Thepresent retractable brush opens to a large size, the bristles thereofdirectly bear on said tissue transversely thereto and are urged furtherinto said tissue by direct pressure. The brush is then rotated to samplea large area while concurrently reaching through the basement membraneto the basal cell layer.

FIG. 1 is a partial perspective and sectional view of an embodiment ofthis invention comprising a brush 10 formed of two separate brushsections 12 and 14 hingedly connected together as at 16 and outwardlybiased by a spring 17 connected to rigid backbones 18 and 19 to whichare attached bristles 20. The bristles 20 could be of differentstructures as in order to be more adapted to the environment in whichthe brushes will be employed. A cylindrical rigid rod 21 passes througha channel 22 in an endoscope 24 having a viewing lens or window 26 shownat the distal end of the endoscope. Endoscopes are commonly providedwith channels through the instrument, such as 22 through which medicalinstruments pass in order to perform certain medical procedures whichare employed in conjunction with the observational aspects of theendoscope 24.

FIG. 2 is similar to FIG. 1 but shows the brush sections 18 and 19 beingurged together against the pressure of spring 17 as the brush biopsydevice of this invention is withdrawn in the endoscope as shown indotted lines 28. Of course, it is understood that FIG. 2 also shows howthe brush 10 opens when it is inserted through channel 22 and spring 17forces the brush sections 12 and 14 to open fully. The area to besampled is maximized by employing the retractable brush structure whichcan be narrow when closed to pass through the endoscope but open fullywhen in position to sample the suspected tissue.

The spring 17 applies a constant biasing force to the brush sections 12and 14. In an equivalent structure, the force opening and closing thebrush need not be continuous and need only be applied to open and closethe brush sections 12 and 14 when they are in the proper position. Therigid rod 21 can be used for this purpose with conventional mechanicalor hydraulic linkage. Before the brush is inserted in the patient, it isin a closed position with a distal front tip 26. The closed brush passesthrough channel. 22, and the brush sections 18 and 19 are opened afterthey pass through the endoscope into the examining area. The rigid rod21 permits direct transverse pressure by the brush bristles against thetissue being examined and enables the brush to be rotated in order toremove cells from the epithelium tissue being examined, arrows 30 and 32indicating the reciprocating and rotational movement at handle 34 whichis transmitted to brush 10 by rod 21. Handle 34 is located at theproximal end. The rigid construction for backbone 17 and 18 assures adirect transfer of force from the user to the brush bristles 20 in orderto effectively operate the brush. The retractable bristles inconjunction with the rigid rod allows a rotating or drilling action tobe employed as desired.

As understood from the above, the bristles of the brush can penetratethrough the basement membrane of the tissue under examination and reachinto the basal cell layer so as to ensure that cells from all threelayers are sampled. When the retractable brush closes either before oras it is withdrawn into the endoscope, the brush bristles also closeretaining the sample cells. After the device is removed from theendoscope the brush again opens permitting the bristles to be wipedacross a suitable carrier for later analysis of the cells deposited onthe carrier.

The brush 10 is illustrative of a tissue removing structure, and othertissue removing structures may be employed. The size of the brush can bevaried; the number and structure of bristles can be varied; theretractable brush structure can be varied so that more than one pair ofbristles may be employed, all of which would be available to one ofordinary skill in the art seeking to utilize the presentnon-lacerational cell sampling technique in conjunction with anendoscope. In essence, the retractable front end brush allowingnon-lacerational removal of tissue from a desired area by manipulationof a rigid rod passing through a channel in an endoscope providesenhanced benefits to patients who may have suspected lesions withouthaving to perform lacerational biopsies on such patients.

Having described this invention with regard to specific embodiments, itis to be understood that the description is not meant as a limitationsince further modifications and variations may be apparent or maysuggest themselves to those skilled in the art. It is intended that thepresent application cover all such modifications and variations as fallwithin the scope of the appended claims.

What is claimed is:
 1. An apparatus for use in conjunction with anendoscope, said endoscope comprising a channel extending the length ofthe endoscope; said endoscope being sized to fit into the nasopharynx,hypopharynx, pharynx, trachea, larynx, or the upper esophagus areas of apatient; said apparatus comprising a rod passing through said channelhaving a distal and a proximal end; a retractable non-lacerationaltissue remover having closed and open positions, said tissue removerattached to the distal end of said rod, said tissue remover being in aclosed position as said rod passes through said endoscope, and a forceapplied to said tissue remover to open said tissue remover after itpasses through said channel, said tissue remover bearing transverselyagainst the tissue being examined and being controlled by said rod toremove tissue from a tissue area being examined, said tissue removercomprising means to non-lacerationally remove cells from at least twocontiguous tissue layers in said nasopharynx, hypopharynx, pharynx,trachea, larynx, or the upper esophagus areas of a patient; saidretractable tissue remover being closed before being withdrawn from saidendoscope, so as to retain the collected cells and remove them as theclosed tissue remover is withdrawn from the endoscope.
 2. An apparatusas set forth in claim 1, wherein said tissue remover comprises aretractable brush.
 3. An apparatus as set forth in claim 2, wherein saidretractable brush comprises a pair of bristle structures hingedly joinedtogether by a biasing force biasing said pair of bristles open to beartransversely against the tissue being examined.
 4. An apparatus as setforth in claim 1, wherein said rod is rigid, said retractablenon-lacerational tissue remover being in a closed position to passthrough said channel, said rod being manipulated to open said tissueremover after it passes through said channel in order to remove tissue.5. An apparatus as set forth in claim 2, wherein said rod is rigid. 6.An apparatus as set forth in claim 5, wherein said retractable brush isopened after being withdrawn from said endoscope to allow collection ofcells therefrom.
 7. An apparatus as set forth in claim 1, wherein saidchannel is interior to said endoscope.
 8. An apparatus as set forth inclaim 3, wherein said bristle structure of each member of said pair ofsaid bristle structures comprises substantially similar structure.
 9. Anapparatus as set forth in claim 3, further comprising a spring hingedlyjoining said bristle structures, said spring bearing said bristlestructures to a full open position.
 10. An apparatus for use inconjunction with an endoscope to examine tissue cells located within andbelow a keratinized layer, said endoscope comprising a channel extendingthe length of the endoscope; said endoscope being sized to fit in thenasopharynx, hypopharynx, pharynx, trachea, larynx, or the upperesophagus areas of a patient; said apparatus comprising a rod passingthrough said channel having a distal and a proximal end; a retractablenon-lacerational tissue remover attached to the distal end of said rod,said tissue remover comprising a brushing apparatus which is movable tobear against the tissue being examined and being controlled by said rodto remove tissue from a tissue area being examined, said brushingapparatus comprising bristles which exert sufficient pressure todislodge cells in and under said keratinized layer in said nasopharynx,hypopharynx, pharynx, trachea, larynx, or the upper esophagus areas of apatient.
 11. An apparatus as set forth in claim 10, wherein said tissuecells exist in superficial, intermediate and basal layers, said bristlespenetrating into at least said superficial and intermediate layers. 12.An apparatus as set forth in claim 10, wherein said bristles penetrateinto said basal layer.
 13. An apparatus as set forth in claim 10,wherein said keratinized layer comprises multiple layers of keratinizedcells, said bristles penetrating said multiple layers.